27.1: Classification of Amino Acids. Chapter 27: Amino Acids, Peptides, and Proteins. monomer unit:...
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Transcript of 27.1: Classification of Amino Acids. Chapter 27: Amino Acids, Peptides, and Proteins. monomer unit:...
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Chapter 27: Amino Acids, Peptides, and Proteins. monomer unit: α-amino acids
Biopolymer: the monomeric amino acids are linked through an amide bond (the carboxylic acids of one AA with the α-amino group of a second)
peptide (< 50 amino acids) protein (> 50 amino acids)
R CO2H
NH2H
!- Amino Acid
R = sidechain
R1
H3N CO2
R2
H3N CO2
+ - H2O R1
H3N
H N
O
CO2
R2
C-terminus
N-terminus
Peptide or protein (polypeptide)
N H
O
R3
H N
O
R2
N H
O
R1
H N
N H
O
R7
H N
O
R6
N H
O
R5
R4 H N
O
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27.1: Classification of Amino Acids. AA’s are classified according to the location of the amino group.
There are 20 genetically encoded α-amino acids found in peptides and proteins
19 are primary amines, 1 (proline) is a secondary amine 19 are “chiral”, 1 (glycine) is achiral; the natural configuration of the α-carbon is L.
!-amino acid (2-amino carboxylic acid)
C CO2HH2N
H
H
C CO2HC
H
H
H2N
H
H
C CC
H
H
H2N
H
H
CO2H
H
H
"-amino acid (3-amino carboxylic acid)
#-amino acid (4-amino carboxylic acid)
CO2H
CH3
H2N H
CO2H
R
H2N H
L-alanine
CHO
HO H
H OH
CH2OH
CHO
H OH
HO H
CH2OH
L-erythroseD-erythrose
CO2H
H2N H
H OH
CH3
CO2H
H2N H
H3C H
CH2CH3
L-theronine (2S,3R)
L-isoleucine (2S,3S)
CHO
CH2OH
H OH
D-glyceraldehyde
CHO
CH2OH
HO H
L-glyceraldehyde
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α-Amino acids are classified by the properties of their sidechains. Nonpolar:
(S)-(+)-Valine (Val, V)
(S)-(–)-Tryptophan (Trp, W)(S)-(–)-Proline (Pro, P) (S)-(–)-Phenylalanine (Phe, F)
COO–
NH3
H
N
H
COO–
NH3
COO–
NH3
COO–
NH3
NH3
COO–
COO–
(2S,3S)-(+)-Isoleucine (Ile, I)
(S)-(+)-Alanine (Ala, A)
(S)-(–)-Leucine (Leu, L)
Glycine (Gly, G)
NH3
COO–
COO–
NH3N H
NH3
COO–S
(S)-(–)-Methionine (Met, M)
Polar but non-ionizable:
(S)-(+)-Glutamine (Gln, Q)
H2N
O
NH3
COO–
(S)-(–)-Tyrosine (Tyr, Y)(2S,3R)-(–)-Threonine (Thr, T)(S)-(–)-Serine (Ser, S)
COO–
NH3
COO–
NH3
COO–
NH3 NH3
COO–
NH3
COO–
O
H2NHS
HO
OH
HO
(R)-(–)-Cysteine (Cys, C) (S)-(–)-Asparagine (Asn, N)
pKa ~ 13 pKa ~ 13
pKa ~ 8.2
pKa ~ 10.1
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Acidic:
Basic:
(S)-(–)-Histidine (His, H)
NH3
COO– COO–
NH3 NH3
COO– N
H
N N
H
H
(S)-(+)-Lysine (Lys, K) (S)-(+)-Arginine (Arg, R)
pKa ~ 10.5 pKa ~ 6.0 pKa ~ 12.5
H2N
N H H
H3N
-O
O NH3
COO–
(S)-(+)-Aspartic Acid (Asp, D)
COO–
NH3
O
-O
(S)-(+)-Glutamic Acid (Glu, E)
pKa ~ 3.6 pKa ~ 4.2
27.2: Stereochemistry of Amino Acids: The natural configuration of the α-carbon is L. D-Amino acids are found in the cell walls of bacteria. The D-amino acids are not genetically encoded, but derived from the epimerization of L-isomers
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27.3: Acid-Base Behavior of Amino Acids. Amino acids exist as a zwitterion: a dipolar ion having both a formal positive and formal negative charge (overall charge neutral).
CO2H
R
H
H2N CO2
R
H
H3N _+
Amino acids are amphoteric: they can react as either an acid or a base. Ammonium ion acts as an acid, the carboxylate as a base.
Isoelectric point (pI): The pH at which the amino acid exists largely in a neutral, zwitterionic form (influenced by the nature of the sidechain)
pKa ~ 5 pKa ~ 9
CO2
R
H
H3N _+CO2H
R
H
H3N +
CO2
R
H
H2N HO
_
pKa2 low pH high pH
_H3O +
pKa1
Table 27.2 (p. 1115) & 27.2 (p. 1116)
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pI = pKax + pKay
2
CO2
CH3
H
H3NCO2H
CH3
H
H3N
low pH
CO2
CH3
H
H2N + +
high pH
pKa1 (2.3)
pKa2 (9.7)
CO2H
CH2
H
H3N
CO2H
pKa3 (3.6)
CO2
H
H3N
CH2
CO2H
CO2
H
H3N
CH2
CO2
pKa2 (9.6)
pKa1 (1.9)
CO2
H
H2N
CH2
CO2
low pH high pH
CO2H
(CH2)4
H
H3N
NH3
pKa2 (9.0)
CO2
H
H3N
(CH2)4
NH3
CO2
H
H2N
(CH2)4
NH3
pKa3 (10.5)
pKa1 (2.2)
CO2
H
H2N
(CH2)4
NH2
low pH high pH
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Electrophoresis: separation of polar compounds based on their mobility through a solid support. The separation is based on charge (pI) or molecular mass.
+ _
_ _ _ _ + + + +
+ _
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Strecker Synthesis: recall reductive amination
C CO2HR
O NH3
C CO2HR
NH2
H
NaB(CN)H3
R C CO2H
NH2
H
C HR
O NH3
C HR
NH2 NaC!N
N!C:
R C C!N
NH2
H
H3O +
-or- NaOH, H2O
R C CO2H
NH2
H
Amidomalonate Synthesis: recall the malonic acid synthesis
H CO2Et C
CO2EtHN EtO Na
RCH2X
H3O
- CO2 RCH2 CO2H C
HH2N
O
RCH2 CO2Et C
CO2EtHN
O
R-CH2-CO2H R C CO2H
Br
R C CO2H
NH2 Br2, PBr3 NH3
H H
27.5: Synthesis of Amino Acids:
Ch. 19.16
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R CO2
H3N H H3C O CH3
O O
base R CO2H
HN H
O
H3C
HOCH2CH3
H+R CO2CH2CH3
H2N H
27.6: Some Biochemical Reactions of Amino Acids. Many enzymes involved in amino acid biosynthesis, metabolism and catabolism are pyridoxal phosphate (vitamin B6) dependent (please read)
NH3
R CO2 -
H
L-amino acid
NH3
R H CO2
-
D-amino acid
racemase, epimerase
H3N
R H
H
decarboxylase
O
R CO2 -
transaminase
N
2-O3PO OH
O H
pyridoxal phosphate (PLP)
+
N H
PO
N
OH
CO2 -R
27.5: Reactions of Amino Acids. Amino acids will undergo reactions characteristic of the amino (amide formation) and carboxylic acid (ester formation) groups.
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27.7: Peptides. Proteins and peptides are polymers made up of amino acid units (residues) that are linked together through the formation of amide bonds (peptide bonds) from the amino group of one residue and the carboxylate of a second residue
By convention, peptide sequences are written left to right from the N-terminus to the C-terminus
H2N CO2H
Alanine
H2N CO2H
HO
Serine
+ - H2O H2N
H N
O
CO2H
OH
Ala - Ser (A - S)- H2O
H2N
H N
O
CO2H
HO
Ser - Ala (S - A)
C-terminus
N-terminus
C-terminus
N-terminus
N H
O
R3
H N
O
R2
N H
O
R1
H N
N H
O
R7
H N
O
R6
N H
O
R5
R4 H N
O
backbone
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The amide (peptide) bond has C=N double bond character due to resonance resulting in a planar geometry
restricts rotations resistant to hydrolysis
R1
H N
N
O R2 H N
O
amide bond
R1
H N
N
O R2 H N
O
_
+
H H
The N-H bond of one amide linkage can form a hydrogen bond with the C=O of another.
N
N
O
H
R
O
H
N
N
O
H
R
O
H
N
N
O
H
R
O
H
N-O distance 2.85 - 3.20 Å optimal N-H-O angle is 180 °
Disulfide bonds: the thiol groups of cysteine can be oxidized to form disulfides (Cys-S-S-Cys)
SH HO2C
NH2 2
1/2 O2 H2O
S HO2C
NH2
S CO2H
NH2H2
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N H
O
R2
H N
O
R1
N H
H N
O
R5
N H
O
R4
H N
O
N H
O H N
O
R6
N H
H N